Chronic Administration of Exogenous Lactate Increases Energy Expenditure during Exercise through Activation of Skeletal Muscle Energy Utilization Capacity in Mice.

We compared the effects of chronic exogenous lactate and exercise training, which influence energy substrate utilization and body composition improvements at rest and during exercise, and investigated the availability of lactate as a metabolic regulator. The mice were divided into four groups: CON (sedentary + saline), LAC (sedentary + lactate), EXE (exercise + saline), and EXLA (exercise + lactate). The total experimental period was set at 4 weeks, the training intensity was set at 60-70% VO2max, and each exercise group was administered a solution immediately after exercise. Changes in the energy substrate utilization at rest and during exercise, the protein levels related to energy substrate utilization in skeletal muscles, and the body composition were measured. Lactate intake and exercise increased carbohydrate oxidation as a substrate during exercise, leading to an increased energy expenditure and increased protein levels of citrate synthase and malate dehydrogenase 2, key factors in the TCA(tricarboxylic acid) cycle of skeletal muscle. Exercise, but not lactate intake, induced the upregulation of the skeletal muscle glucose transport factor 4 and a reduction in body fat. Hence, chronic lactate administration, as a metabolic regulator, influenced energy substrate utilization by the skeletal muscle and increased energy expenditure during exercise through the activation of carbohydrate metabolism-related factors. Therefore, exogenous lactate holds potential as a metabolic regulator.

Oyster (Ostrea Plicatula Gmelin) Peptides Improve Exercise Endurance Capacity via Activating AMPK and HO-1.

OBJECTIVE: Previous studies have shown that oyster peptides (OPs) have antioxidant and anti-fatigue activities. This study aimed to investigate the effects of OPs on swimming endurance in mice and the underlying mechanisms. METHODS: The mice were subjected to gavage with OPs and subjected to exercise training. After 14 days, various biochemical indicators in the blood and gastrocnemius muscle of mice were assessed, and real-time PCR was utilized to detect the level of signal pathway regulation by OPs in the gastrocnemius muscle. Molecular docking technology was employed to observe the potential active components in OPs that regulate signal pathways. RESULTS: In this study, OPs supplementation combined with and without exercise significantly extended swimming time compared to the sedentary group. OPs supplementation with exercise also increased glycogen levels and decreased blood urea nitrogen, lactate dehydrogenase, and lactic acid levels. Additionally, mice in the exercise with OPs group exhibited higher activities of antioxidant enzymes. OPs can upregulate metabolic regulatory factors such as AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma coactivator-1 alpha, peroxisome proliferator-activated receptor delta, and glucose transporter 4, thereby increasing energy supply during exercise. Additionally, OPs enhances the expression of heme oxygenase 1 and superoxide dismutase 2, thereby reducing oxidative stress during physical activity. Molecular docking analyses revealed that peptides found in OPs formed hydrogen bonds with AMPK and HO-1, indicating that they can exert bioactivity by activating target proteins such as AMPK and HO-1. CONCLUSIONS: OPs supplementation improved energy reserves, modulated energy metabolism pathways, and coordinated antioxidative stress responses, ultimately enhancing swimming endurance. These findings suggest that OPs have the potential to improve exercise levels by promoting metabolism and improving energy utilization efficiency.

Metabolomics of astaxanthin biosynthesis and corresponding regulation strategies in Phaffia rhodozyma.

Astaxanthin is a valuable carotenoid and is used as antioxidant and health care. Phaffia rhodozyma is a potential strain for the biosynthesis of astaxanthin. The unclear metabolic characteristics of P. rhodozyma at different metabolic stages hinder astaxanthin's promotion. This study is conducted to investigate metabolite changes based on quadrupole time-of-flight mass spectrometry metabolomics method. The results showed that the downregulation of purine, pyrimidine, amino acid synthesis, and glycolytic pathways contributed to astaxanthin biosynthesis. Meanwhile, the upregulation of lipid metabolites contributed to astaxanthin accumulation. Therefore, the regulation strategies were proposed based on this. The addition of sodium orthovanadate inhibited the amino acid pathway to increase astaxanthin concentration by 19.2%. And the addition of melatonin promoted lipid metabolism to increase the astaxanthin concentration by 30.3%. It further confirmed that inhibition of amino acid metabolism and promotion of lipid metabolism were beneficial for astaxanthin biosynthesis of P. rhodozyma. It is helpful in understanding metabolic pathways affecting astaxanthin of P. rhodozyma and provides regulatory strategies for metabolism.

Lactate Activates AMPK Remodeling of the Cellular Metabolic Profile and Promotes the Proliferation and Differentiation of C2C12 Myoblasts.

Lactate is a general compound fuel serving as the fulcrum of metabolism, which is produced from glycolysis and shuttles between different cells, tissues and organs. Lactate is usually accumulated abundantly in muscles during exercise. It remains unclear whether lactate plays an important role in the metabolism of muscle cells. In this research, we assessed the effects of lactate on myoblasts and clarified the underlying metabolic mechanisms through NMR-based metabonomic profiling. Lactate treatment promoted the proliferation and differentiation of myoblasts, as indicated by significantly enhanced expression levels of the proteins related to cellular proliferation and differentiation, including p-AKT, p-ERK, MyoD and myogenin. Moreover, lactate treatment profoundly regulated metabolisms in myoblasts by promoting the intake and intracellular utilization of lactate, activating the TCA cycle, and thereby increasing energy production. For the first time, we found that lactate treatment evidently promotes AMPK signaling as reflected by the elevated expression levels of p-AMPK and p-ACC. Our results showed that lactate as a metabolic regulator activates AMPK, remodeling the cellular metabolic profile, and thereby promoting the proliferation and differentiation of myoblasts. This study elucidates molecular mechanisms underlying the effects of lactate on skeletal muscle in vitro and may be of benefit to the exploration of lactate acting as a metabolic regulator.

Creatine in T Cell Antitumor Immunity and Cancer Immunotherapy.

Creatine is a broadly used dietary supplement that has been extensively studied for its benefit on the musculoskeletal system. Yet, there is limited knowledge regarding the metabolic regulation of creatine in cells beyond the muscle. New insights concerning various regulatory functions for creatine in other physiological systems are developing. Here, we highlight the latest advances in understanding creatine regulation of T cell antitumor immunity, a topic that has previously gained little attention in the creatine research field. Creatine has been identified as an important metabolic regulator conserving bioenergy to power CD8 T cell antitumor reactivity in a tumor microenvironment; creatine supplementation has been shown to enhance antitumor T cell immunity in multiple preclinical mouse tumor models and, importantly, to synergize with other cancer immunotherapy modalities, such as the PD-1/PD-L1 blockade therapy, to improve antitumor efficacy. The potential application of creatine supplementation for cancer immunotherapy and the relevant considerations are discussed.

Fibroblast growth factor 21 regulates browning of white fat: The role of exercise / 中国组织工程研究

BACKGROUND: Fibroblast growth factor 21 (FGF-21) is a newly discovered metabolic regulator that has been expressed in various tissues and organs such as liver, fat and skeletal muscle. Numerous studies have shown that FGF-21 is involved in the browning of white fat, but there is less review of this aspect worldwide. Especially the mediation of exercise is still controversial. OBJECTIVE: To explore the inducing factors and mechanism of FGF-21 regulating the browning of white fat, especially the effects of exercise on it, in order to provide new targets for the treatment of obesity and related metabolic diseases. METHODS: A computer-based search of CNKI and PubMed databases was performed for relevant articles published from January 2001 to July 2019 using the keywords of “FGF-21, browning, exercise, fat” in Chinese and English, respectively. Finally, 45 eligible articles were included in results analysis according to the inclusion criteria. RESULTS AND CONCLUSION: FGF-21 can enter the blood in autocrine, endocrine and paracrine patterns to regulate glycolipid metabolism, improve insulin resistance, prevent liver disease, and promote the browning of white fat. Exercise can induce the secretion and expression of FGF-21, thereby effectively regulating the activation of brown fat and browning of white fat to achieve fat loss. Due to differences in exercise patterns, exercise intensity, and exercise time, the current process of exercise-mediated FGF-21 involvement in the browning of white fat needs further study.

The Multiple Roles of XBP1 in Regulation of Glucose and Lipid Metabolism.

X-box binding protein1 (XBP1) especially exerts its fundamental effects in the cellular organelle endoplasmic reticulum (ER) via affecting three trans-membrane stress sensor proteins: PKRlike ER kinase (PERK), inositol-requiring enzyme 1(IRE1) and activating transcription factor 6(ATF6). At the center of XBP1's broad effects is its remarkable metabolic housekeeper function. XBP1 decreased glucose dysfunction via funneling its effects on improving insulin sensitivity and stimulating insulin secretion. However, XBP1 also yields its double-edged effects, driving the transformation from excess glucose to lipid, which is a key contribution to obesity and T2DM. In this review, we highlight the vital mechanism of XBP1 in manipulating glucose and lipid metabolism involved by multiple signaling pathways.